The overall objective of this study is to investigate coordination of intracellular activity in mammary gland and to determine how the activities of the cellular compartments are coordinated during alterations in cellular function. Close examination of the metabolic characteristics of the mitochondria, the cytosol, and their interaction in all of the physiological stages of the gland will help to reveal the sites and mechanism of regulation. We have demonstrated that the activities of the mitochondrial and cytosolic compartments of the mammary gland cells are coordinated and that the relationship between them changes during the transition of the gland from the pregnant to the lactating state. The site of the modulation of this relationship between the intracellular compartments appears not to be the facilitated transfer of anionic substrates across the mitochondrial membrane, but the formation and utilization of these metabolites in the cytosol or mitochondria. The mechanism responsible for the changes in substrate concentrations is still unresolved. Obviously, the enzyme systems forming and utilizing these molecules are likely candidates. In the coming year, we will focus our investigations on these enzyme systems. BIBLIOGRAPHIC REFERENCES: Bartley, J.C., S. Barber, and S. Abraham (1975) Identity, Release, and Binding of Mitochondrial Bound Hexokinases in Mammary Glands and Adenocarcinomas of Lactating Mice, Cancer Res. 35:1649-1653.